Cryptosporidium parvum regulation of human epithelial cell gene expression
Cryptosporidium parvum regulation of human epithelial cell gene expression
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DOI：
10.1016/j.ijpara.2003.10.001
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Abrahamsen, MS
中科院分区：
文献类型：
--
作者：
Deng, MQ;Lancto, CA;Abrahamsen, MS
小隐孢子虫是一种专性细胞内原生动物，能够在免疫功能低下的个体中引起危及生命的腹泻病。由于缺乏对感染发病机制的了解，开发新治疗策略的努力受到阻碍。为了更好地了解宿主对微小隐球菌感染的反应，使用含有 12,600 个人类基因探针组的 Affymetrix 寡核苷酸 microaffays 分析了受感染的人类回盲部腺癌细胞的基因表达谱。对三个独立实验的表达数据进行统计分析，确定了 223 个基因，其表达在接种后 24 小时时受到小隐孢子虫感染的可重复调节（125 个上调，98 个下调），其中 13 个通过定量逆转录酶聚合酶链反应分析进行了验证。该分析揭示了宿主热休克基因和促炎趋化因子 IL-8、RANTES 和 SCYB5 基因的一致上调。宿主肌动蛋白和微管蛋白基因的多个基因上调，而肌动蛋白结合蛋白的基因下调，证实了先前观察到的响应小隐孢子虫感染的宿主细胞骨架重排的观察结果。此外，与细胞增殖和凋亡相关的宿主基因受到差异性调节，反映了宿主-寄生虫相互作用的复杂性。总之，这项研究表明，微小念珠菌感染会导致宿主生化途径发生显着变化，并为细胞内原生动物寄生虫引起的传染病的特定生物学过程提供新的见解。 (C) 2004 年代表澳大利亚寄生虫学协会。由 Elsevier Ltd 出版。保留所有权利。
Cryptosporidium parvum is an obligate intracellular protozoan capable of causing life-threatening diarrhoeal disease in immunocompromised individuals. Efforts to develop novel therapeutic strategies have been hampered by the lack of understanding of the pathogenesis of infection. To better understand the host response to C parvum infection, gene expression profiles of infected human ileocecal adenocarcinoma cells were analysed by using Affymetrix oligonucleotide microaffays containing probe sets for 12,600 human genes. Statistical analysis of expression data from three independent experiments identified 223 genes whose expression was reproducibly regulated by C parvum infection at 24 h post-inoculation (125 up-regulated and 98 down-regulated), 13 of which were validated by quantitative reverse transcriptase polymerase chain reaction analysis. This analysis revealed the consistent up-regulation of host heat-shock genes and genes for pro-inflammatory chemokines IL-8, RANTES, and SCYB5. Multiple genes for host actin and tubulin genes were up-regulated whereas genes for actin binding proteins were down-regulated, confirming previous observations of host cytoskeleton rearrangement in response to C. parvum infection. In addition, host genes associated with cell proliferation and apoptosis were differentially regulated, reflecting the complexity of host-parasite interaction. Together, this study demonstrated that C parvum infection results in significant changes in host biochemical pathways and provides new insights into specific biological processes of infectious disease caused by an intracellular protozoan parasite. (C) 2004 on behalf of Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.